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Endogenous T cell activation relies on recognizing tumor‐specific antigens. However, tumor cells often alter phenotypes to evade immune surveillance, resulting in immune escape and drug resistance. Photodynamic therapy (PDT) activates anti‐tumor immune responses by generating reactive oxygen species, which induce endoplasmic reticulum stress and immunogenic cell death. The clinical application of PDT is limited by immunosuppressive tumor microenvironment. Notably, enhancer of zeste homolog 2 (EZH2) regulates expression of immune‐related genes in tumor and immune cells through H3K27 methylation. Consequently, targeting EZH2‐mediated epigenetic silence provides an effective strategy to enhance the anti‐tumor immune effect of PDT. In this study, a nano‐delivery system (NP2) is designed to demonstrate PDT and epigenetic reprogramming effects. NP2 can reverse epigenetic silence, enhance MHC‐I expression, and induce release of CXCL9‐10 via EZH2i. Meanwhile, NP2 has a significant effect on PDT, inducing endoplasmic reticulum stress that resulted in immunogenic cell death and subsequent activation of the immune cascade. In a mouse model of in situ breast cancer, the combination of PDT activation and epigenetic reprogramming through EZH2i showed synergistic effects on remolding, and triggering a robust anti‐tumor immune response in vivo. This study provides a novel idea for improving the immunosuppressive environment in clinical individualized immunotherapy. [ABSTRACT FROM AUTHOR]

Lung cancer has the highest fatality rate among malignant tumors in the world. Finding new biomarkers of drug resistance is of great importance in the prognosis of lung cancer patients. We found that the polymorphisms of Adenylate Cyclase 1 (ADCY1) are significantly associated with platinum-based chemotherapy resistance in lung cancer patients in our previous research. In this study, we wanted to identify the mechanism of ADCY1 affecting platinum resistance. We used an MTT assay to find if the expression of ADCY1 is associated with the sensitivity of cisplatin in A549, H1299, and A549-DDP cells. Then, we performed CCK-8 tests to detect the absorbance of these cells stimulated by ADCY1, which can discover the cell proliferation that is affected by ADCY1. We investigated cell apoptosis and cell cycles regulated by ADCY1 through the flow cytometry assay. RNA sequencing was used to find the downstream genes affected by ADCY1 which may be associated with drug resistance in lung cancer patients. ADCY1 has higher expression in lung cancer cells than in normal cells. ADCY1 can affect cisplatin resistance in lung cancer cells by regulating cell proliferation, cell apoptosis, and the cell cycle. It may control cell apoptosis by regulating the classical apoptosis biomarkers Bax and Bcl2. Our study showed that ADCY1 may be a new biomarker in the prognosis of lung cancer patients. Much work remains to be carried out to clarify the mechanism in this important emerging field. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti‐epileptic drugs (AEDs), drug‐refractory epilepsy develops in about one‐third of patients, highlighting the need for alternative therapeutic approaches. Aims: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. Methods: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate‐induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK‐8 assay, flow cytometry, RT‐PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid‐ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. Results: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA‐induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate‐induced HT22 cell damage model, 2.5 μM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid‐ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti‐ferroptotic effect of TGZ was confirmed in an erastin‐induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. Conclusion: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti‐ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments. [ABSTRACT FROM AUTHOR]